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Journal of Ginseng Research May 2023Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while...
BACKGROUND
Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD.
METHODS
Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo.
RESULTS
We identified ginsenosides Rc as a novel activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates -mediated fatty acid oxidation in vivo and in vitro. Hepatic specific deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD.
CONCLUSION
Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving -mediated fatty acid oxidation and antioxidant capacity in a dependent manner, and providing a promising strategy for NAFLD.
PubMed: 37252281
DOI: 10.1016/j.jgr.2020.07.005 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Aug 2022To evaluate the efficacy and safety of antidepressants in treatment of depression disorder in children and adolescents by network meta-analysis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of antidepressants in treatment of depression disorder in children and adolescents by network meta-analysis.
METHODS
Databases of PubMed, Cochrane Library, EMBASE, Web of Science, PsycINFO, CBM, CNKI and Wanfang Data were searched for randomized controlled trials (RCT) related to antidepressants in treatment of children and adolescents with depression from inception to December 2021. Quality assessment and data extraction from the included RCTs were performed. Statistical analyses of efficacy and tolerability were conducted with Stata 15.1 software. Surface under the cumulative ranking (SUCAR) was used to rank the value of the antidepressants.
RESULTS
A total of 33 RCTs were included in 32 articles, involving 6949 patients. There are 13 antidepressants used in total, including amitriptyline, vilazodone, fluoxetine, selegiline, paroxetine, imipramine, desipramine, sertraline, nortriptyline, escitalopram, citalopram, venlafaxine and duloxetine. The results of network meta-analysis showed that the efficacy of duloxetine ( =1.95, 95% 1.41-2.69), fluoxetine ( =1.73, 95% 1.40-2.14), venlafaxine ( =1.37, 95% 1.04-1.80) and escitalopram ( =1.48, 95% : 1.12-1.95) were significantly higher than that of placebos (all <0.05); the probability cumulative ranks were duloxetine (87.0%), amitriptyline (83.3%), fluoxetine (79.0%), escitalopram (62.7%), etc. The results showed that the intolerability of patients receiving imipramine ( =0.15, 95% 0.08-0.27), sertraline ( =0.33, 95% 0.16-0.71), venlafaxine ( =0.35, 95% 0.17-0.72), duloxetine ( =0.35, 95% 0.17-0.73) and paroxetine ( =0.52, 95% 0.30-0.88) were significantly higher than that of placebos (all <0.05), and the probability cumulative ranks were imipramine (95.7%), sertraline (69.6%), venlafaxine (68.6%), duloxetine (68.2%), etc. Conclusion: Among 13 antidepressants, duloxetine, fluoxetine, escitalopram and venlafaxine are significantly better than placebo in terms of efficacy, but duloxetine and venlafaxine are less well tolerated.
Topics: Adolescent; Child; Humans; Venlafaxine Hydrochloride; Duloxetine Hydrochloride; Fluoxetine; Sertraline; Paroxetine; Amitriptyline; Imipramine; Depression; Escitalopram; Network Meta-Analysis; Depressive Disorder, Major; Antidepressive Agents
PubMed: 37202104
DOI: 10.3724/zdxbyxb-2022-0145 -
PloS One 2023There is significant overlap between non-alcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD) with regards to risk factors and disease...
BACKGROUND AND AIMS
There is significant overlap between non-alcoholic fatty liver disease (NAFLD) and alcohol-associated liver disease (ALD) with regards to risk factors and disease progression. However, the mechanism by which fatty liver disease arises from concomitant obesity and overconsumption of alcohol (syndrome of metabolic and alcohol-associated fatty liver disease; SMAFLD), is not fully understood.
METHODS
Male C57BL6/J mice were fed chow diet (Chow) or high-fructose, high-fat, high-cholesterol diet (FFC) for 4 weeks, then administered either saline or ethanol (EtOH, 5% in drinking water) for another 12 weeks. The EtOH treatment also consisted of a weekly 2.5 g EtOH/kg body weight gavage. Markers for lipid regulation, oxidative stress, inflammation, and fibrosis were measured by RT-qPCR, RNA-seq, Western blot, and metabolomics.
RESULTS
Combined FFC-EtOH induced more body weight gain, glucose intolerance, steatosis, and hepatomegaly compared to Chow, EtOH, or FFC. Glucose intolerance by FFC-EtOH was associated with decreased hepatic protein kinase B (AKT) protein expression and increased gluconeogenic gene expression. FFC-EtOH increased hepatic triglyceride and ceramide levels, plasma leptin levels, hepatic Perilipin 2 protein expression, and decreased lipolytic gene expression. FFC and FFC-EtOH also increased AMP-activated protein kinase (AMPK) activation. Finally, FFC-EtOH enriched the hepatic transcriptome for genes involved in immune response and lipid metabolism.
CONCLUSIONS
In our model of early SMAFLD, we observed that the combination of an obesogenic diet and alcohol caused more weight gain, promoted glucose intolerance, and contributed to steatosis by dysregulating leptin/AMPK signaling. Our model demonstrates that the combination of an obesogenic diet with a chronic-binge pattern alcohol intake is worse than either insult alone.
Topics: Mice; Animals; Male; Leptin; Diet, Western; Glucose Intolerance; AMP-Activated Protein Kinases; Ethanol; Liver; Liver Diseases, Alcoholic; Non-alcoholic Fatty Liver Disease; Obesity; Lipid Metabolism; Diet, High-Fat; Mice, Inbred C57BL
PubMed: 37134024
DOI: 10.1371/journal.pone.0281954 -
Social Psychiatry and Psychiatric... Oct 2023The self-medication hypothesis suggests people may develop Alcohol Use Disorder (AUD) or Non-Alcohol Substance Use Disorder (NA-SUD) following PTSD as a maladaptive way...
PURPOSE
The self-medication hypothesis suggests people may develop Alcohol Use Disorder (AUD) or Non-Alcohol Substance Use Disorder (NA-SUD) following PTSD as a maladaptive way of coping with PTSD symptoms. Given that an accumulation of trauma experiences and interpersonal trauma increase the likelihood and severity of PTSD, we sought to determine whether the number and type of traumas additionally predict AUD and NA-SUD following PTSD.
METHODS
We analysed data from 36,309 adult participants in the National Epidemiologic Survey on Alcohol and Related Conditions-III (NESARC-III) study (M = 45.63 years, SD = 17.53, 56.3% female) who were administered semi-structured diagnostic interviews of trauma exposure and PTSD, AUD and NA-SUD symptoms.
RESULTS
Individuals with PTSD were more likely to have an AUD or NA-SUD than those without PTSD. Endorsement of a greater number of traumas was associated with greater odds of having PTSD, AUD, or NA-SUD. Experience of interpersonal trauma was related to greater odds of having PTSD and subsequent AUD or NA-SUD than not experiencing interpersonal trauma. Multiple experiences of interpersonal trauma compared to one interpersonal trauma exposure also increased the odds of having PTSD followed by AUD or NA-SUD.
CONCLUSIONS
Interpersonal trauma and multiple experiences of interpersonal trauma may result in individuals turning to alcohol and substances as a way to alleviate intolerable PTSD symptomology, aligning with the self-medication hypothesis. Our findings highlight the importance of ensuring services and support for interpersonal trauma survivors and for those who have experienced multiple traumas given their increased for unfavourable outcomes.
Topics: Adult; Humans; Female; Male; Stress Disorders, Post-Traumatic; Substance-Related Disorders; Alcohol-Related Disorders; Alcoholism; Alcohol Drinking
PubMed: 37133523
DOI: 10.1007/s00127-023-02472-6 -
ACS Omega Apr 2023Propolis, one of the most important bee products, cannot be used in its raw form. The efficiency of the bioactive components of propolis increases with the extraction...
Propolis, one of the most important bee products, cannot be used in its raw form. The efficiency of the bioactive components of propolis increases with the extraction process. The choice of solvent to be used in the extraction of propolis is effective in determining the properties of the extract. Ethanol is the most widely used solvent, which significantly increases the efficiency of its bioactive components in the extraction of propolis. Effective nonalcohol-based extraction techniques have become important since alcohol-based extracts cause some discomfort and cannot be used in people with alcohol intolerance. The use of water in propolis extraction is less preferred than ethanol because it does not thoroughly dissolve the bioactive components. In this study, the effect of incorporating hydrogen into solvents (water, ethanol, and methanol) on the extraction of total phenolic content, total flavonoid content, antioxidant activities, and phenolic compound profile of the propolis sample was evaluated. Incorporation of H into water, ethanol, and methanol led to an increase in total phenolic content by 19.08, 5.43, and 12.71% and in the total flavonoid content by 28.97, 17.13, and 2.06%, respectively. Besides, the highest increases in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) scavenging activities were observed in hydrogen-rich water (4.4%) and hydrogen-rich ethanol (32.4%) compared to their counterparts, respectively. On the other hand, incorporation of H into different solvents led to significant increases in different phenolics, and it was observed that the level of change was dependent on the type of the phenolic compound and the solvent used. This study is important in terms of using hydrogen-enriched solvents to extract phenolics from propolis for the first time. Using hydrogen-rich solvents, specifically hydrogen-rich water, was observed to be an effective method for the improvement of phytochemical extraction efficiency in propolis.
PubMed: 37091398
DOI: 10.1021/acsomega.3c01673 -
Biomolecules Mar 2023Accumulating evidence has demonstrated the association between alcohol overconsumption and the development of insulin resistance. However, the underlying mechanisms are...
Accumulating evidence has demonstrated the association between alcohol overconsumption and the development of insulin resistance. However, the underlying mechanisms are not completely understood. To investigate the requirement and sufficiency of hepatocyte toll-like receptor 4 (TLR4) in alcohol-induced insulin resistance, we used two mouse models (Tlr4 and Tlr4) that allow ablation of TLR4 only in hepatocytes (Tlr4) and restoration of endogenous TLR4 expression in hepatocytes on a TLR4-null background (Tlr4 × Alb-Cre), respectively. A Lieber-DeCarli feeding model was used to induce glucose intolerance and insulin resistance in mice. Glucose tolerance test, insulin tolerance test, and insulin signaling experiments were performed to examine systemic and tissue-specific insulin sensitivity. We found that alcohol-fed hepatocyte TLR4 deficient mice (Tlr4) had lower blood glucose levels in response to intraperitoneal injection of insulin. Moreover, increased phosphorylation of glycogen synthase kinase-3β (GSK3β) was observed in the liver of Tlr4 mice after chronic alcohol intake. In contrast, when hepatic TLR4 was reactivated in mice (Tlr4 × Alb-Cre), alcohol feeding caused glucose intolerance in these mice compared with littermate controls (Tlr4). In addition, AKT phosphorylation was dramatically reduced in the liver and epididymal white adipose tissue (eWAT) of alcohol-fed Tlr4 × Alb-Cre mice, which was similar to that of mice with whole-body TLR4 reactivation (Tlr4 × Zp3-Cre). Collectively, these findings suggest that hepatocyte TLR4 is both required and sufficient in the development of insulin resistance induced by alcohol overconsumption.
Topics: Animals; Mice; Ethanol; Glucose Intolerance; Hepatocytes; Insulin; Insulin Resistance; Liver; Mice, Inbred C57BL; Toll-Like Receptor 4
PubMed: 36979389
DOI: 10.3390/biom13030454 -
BMJ Open Diabetes Research & Care Mar 2023The relationship between tea consumption and glucose metabolism remains controversial. This study investigated the associations of tea consumption with impaired glucose...
INTRODUCTION
The relationship between tea consumption and glucose metabolism remains controversial. This study investigated the associations of tea consumption with impaired glucose regulation, insulin secretion and sensitivity in Shanghai High-risk Diabetic Screen project.
RESEARCH DESIGN AND METHODS
A total of 2337 Chinese subjects were enrolled in the study from 2014 to 2019. Each participant conducted a 75 g oral glucose tolerance test (OGTT) with five-point glucose and insulin level examined. They also completed a nurse-administered standard questionnaire including tea, coffee, and alcohol consumption, smoking habit, physical activity, education, sleep quality, etc. RESULTS: The result showed that tea consumption was positively associated with plasma glucose levels during OGTT after adjusting for confounder (Ps <0.05) and was associated with worsening glucose tolerance (OR 1.21, 95% CI 1.01-1.44; p=0.034). Strong tea consumption or long-term tea intake (>10 years) had an increased risk of glucose intolerance (all p<0.05). These associations did not vary in participants drinking green tea. In addition, insulin secretion indexes were decreased 7.0%-13.0% in tea consumption group. Logistic regression analysis showed that tea consumption was independently associated with lower insulin secretion (homeostasis model assessment of β-cell function (HOMA-β) (OR 0.81, 95% CI 0.68-0.97; p=0.021); Stumvoll first-phase index (OR 0.81, 95% CI 0.68-0.97; p=0.020)) in a fully adjusted model. Green tea consumption showed a negative association with insulin secretion (HOMA-β (OR 0.77, 95% CI 0.62-0.96; p=0.019)).
CONCLUSIONS
Tea intake is associated with an increased risk of glucose intolerance in a large high-risk diabetic Chinese population. Habitual tea consumption subjects might have lower pancreatic β-cell function.
Topics: Humans; Glucose Intolerance; Insulin Secretion; Diabetes Mellitus, Type 2; China; Glucose; Tea
PubMed: 36931660
DOI: 10.1136/bmjdrc-2022-003266 -
Genes Jan 2023Camel milk is known for its exceptional medical uses. It has been used since ancient times to treat infant diarrhea, hepatitis, insulin-dependent diabetes (IDDM),...
Camel milk is known for its exceptional medical uses. It has been used since ancient times to treat infant diarrhea, hepatitis, insulin-dependent diabetes (IDDM), lactose intolerance, alcohol-induced liver damage, allergies, and autism. It has the power to treat several diseases, with cancer being the most significant. This study investigated the evolutionary relationship, physiochemical characteristics, and comparative genomic analysis of the casein gene family (CSN1S1, CSN2, CSN1S2, and CSN3) in . Molecular phylogenetics showing the camelid species clustered casein nucleotide sequences into four groups: CSN1S1, CSN2, CSN1S2, and CSN3. The casein proteins from camels were evaluated and found to be unstable, thermostable, and hydrophilic. CSN1S2, CSN2, and CSN3 were acidic, but CSN1S1 was basic. CSN1S1 showed positive selection for one amino acid (Q), CSN1S2 and CSN2 for three (T, K, Q), and CSN3 showed no positive selection. We also compared high-milk-output species such as cattle () and low-milk-yield species such as sheep () with camels () and discovered that YY1 sites are more frequent in sheep than in camels and very low in cattle. We concluded that the ratio of YY1 sites in these species may affect milk production.
Topics: Cattle; Animals; Sheep; Caseins; Camelus; Phylogeny; Milk; Base Sequence; Allergens
PubMed: 36833182
DOI: 10.3390/genes14020256 -
Endocrinology Jan 2023Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that regulates fundamental cellular processes such as proliferation, migration, apoptosis, and differentiation...
Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that regulates fundamental cellular processes such as proliferation, migration, apoptosis, and differentiation through 5 cognate G protein-coupled receptors (S1P1-S1P5). We previously demonstrated that blockade of S1P2 signaling in S1P2-deficient mice attenuates high-fat diet-induced adipocyte hypertrophy and glucose intolerance and an S1P2-specific antagonist JTE-013 inhibits, whereas an S1P1/S1P3 dual antagonist (VPC23019) activates, adipogenic differentiation of preadipocytes. Based on those observations, this study examined whether an S1P1-specific agonist, SEW-2871, VPC23019, or their combination acts on obesity and glucose intolerance in leptin-deficient ob/ob mice. The oral administration of SEW-2871 or JTE-013 induced significant reductions in body/epididymal fat weight gains and epididymal/inguinal fat adipocyte sizes and improved glucose intolerance and adipocyte inflammation in ob/ob mice but not in their control C57BL/6J mice. Both SEW-2871 and JTE-013 decreased messenger RNA levels of tumor necrosis factor-α and CD11c, whereas they increased those of CD206 and adiponectin in the epididymal fats isolated from ob/ob mice with no changes in the levels of peroxisome proliferator activated receptor γ and its regulated genes. By contrast, VPC23019 did not cause any such alterations but counteracted with all those SEW-2871 actions in these mice. In conclusion, the S1P1 agonist SEW-2871 acted like the S1P2 antagonist JTE-013 to reduce body/epididymal fats and improve glucose tolerance in obese mice. Therefore, this study raises the possibility that endogenous S1P could promote obesity/type 2 diabetes through the S1P2, whereas exogenous S1P could act against them through the S1P1.
Topics: Animals; Male; Mice; Diabetes Mellitus, Type 2; Glucose; Glucose Intolerance; Lysophospholipids; Mice, Inbred C57BL; Mice, Obese; Obesity; Receptors, Lysosphingolipid; Sphingosine; Sphingosine-1-Phosphate Receptors
PubMed: 36690339
DOI: 10.1210/endocr/bqad019 -
Bioengineering (Basel, Switzerland) Jan 2023Hyperlipidemia is increasing in prevalence and is highly correlated with cardiovascular disease (CVD). Lipid-lowering medications prevent CVD but may not be suitable...
Hyperlipidemia is increasing in prevalence and is highly correlated with cardiovascular disease (CVD). Lipid-lowering medications prevent CVD but may not be suitable when the side effects are intolerable or hypercholesterolemia is too severe. Double-filtration plasmapheresis (DF) has shown its therapeutic effect on hyperlipidemia, but its side effects are not yet known. We enrolled 45 adults with hyperlipidemia in our study. The sera before and two weeks after DF were evaluated, and we also analyzed perfluorochemicals to see if DF could remove these lipophilic toxins. After DF, all lipid profile components (total cholesterol, triglycerides, high-density lipoprotein [HDL], and low-density lipoprotein [LDL]) had significantly decreased. Leukocyte counts increased while platelet levels decreased, which may have been caused by the puncture wound from DF and consumption of platelets during the process. As for uremic toxins and inflammation, levels of C-reactive protein, uric acid, and alanine transaminase (ALT) all decreased, which may be related to the removal of serum perfluorooctane sulfonate (PFOS) and improvement of renal function. The total cholesterol/HDL ratio and triglycerides were significantly higher in the diabetes mellitus (DM) group at baseline but did not significantly differ after DF. In conclusion, DF showed potential for improving inflammation and removing serum lipids and PFOS in adults with hyperlipidemia.
PubMed: 36671661
DOI: 10.3390/bioengineering10010089